Screening of Clinically Approved and Investigation Drugs as Potential Inhibitors of SARS‐CoV‐2: A Combinedin silicoandin vitroStudy

• DOI: 10.1002/minf.202100062
• Publication Date: 2021-09-16T12:47:03Z
• Authors: Serdar Durdagi; Muge Didem Orhan; Busecan Aksoydan; Seyma Calis; Berna Dogan; Kader Sahin; Aida Shahraki; Necla Birgül Iyison; Timucin Avsar
• Keywords: 0301 basic medicine; Ritonavir; Cefotiam; SARS-CoV-2; Drug Evaluation, Preclinical; Drug Repositioning; Drugs, Investigational; Antiviral Agents; COVID-19 Drug Treatment; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Spike Glycoprotein, Coronavirus; Humans; Angiotensin-Converting Enzyme 2; Coronavirus 3C Proteases

Abstract In the current study, we used 7922 FDA approved small molecule drugs as well compounds in clinical investigation from NIH's NPC database our drug repurposing study. SARS‐CoV‐2 main protease Spike protein/ACE2 targets were virtual screening and top‐100 each docking simulations considered initially short molecular dynamics (MD) their average binding energies calculated by MM/GBSA method. Promising hit selected based on scores then long MD simulations. Based these numerical calculations following found inhibitors for protease: Pinokalant, terlakiren, ritonavir, cefotiam, telinavir, rotigaptide, cefpiramide. addition, 3 identified Spike/ACE2: Denopamine, bometolol, rotigaptide. order to verify predictions of silico analyses, 4 (ritonavir, cefpiramide) 2 (rotigaptide denopamine) Spike/ACE2 interactions tested vitro experiments. While concentration‐dependent inhibition cefotiam was observed protease; denopamine effective at binding.